The present invention relates to a process for dealkylating a substituted amine and is useful in the preparation of a wide variety of amine-containing chemicals.
In the synthesis of many useful chemical compounds comprising amine groups, it is sometimes necessary to protect the amine group from reaction with another functional group in the molecule, or from reaction with a chemical effecting modification of another part of the molecule. This can often be done by preparing a derivative of the amine group from which the original amine group may readily be regenerated. Protection of an amine group in this way has in the past been done by formation of carbamates, amides, imines, enamines and N-hetero atom derivatives.
Another method of amine group protection that is particularly relevant to the present invention is the use of an alkyl group. However, the essence of protection is that the group can be readily removed. While aralkyl groups with the aryl group .alpha. to the nitrogen can be removed by reductive processes, it has been the view that alkyl groups need to contain another functional group to facilitate cleavage of the N-C bond. This subject is fully discussed in "Protective Groups in Organic Synthesis" by T. W. Greene (Wiley & Sons, 1981). Amino group protection is discussed in Chapter 7.
Protection of a primary or secondary amine group using an alkyl group is usually very effective since the alkyl group is, generally speaking, quite inactive in most organic reactions. It is, however, quite difficult to remove for essentially the same reason.
The study of the carbon/nitrogen bond of amines has been the subject of study in recent years. For example, Murahashi and Watanabe disclosed the transition metal catalyzed hydrolysis of tertiary amines with water in an article entitled "Palladium Catalyzed Hydrolysis of Tertiary Amines With Water" published in the Journal of the American Chemical Society 101, 7429 (1979). In this publication it was reported that catalytic oxidation of tertiary amines in the absence of oxygen proceeded generally and efficiently with palladium catalysts to provide secondary amines and carbonyl compounds.
U.S. Pat. No. 4,442,041 to Subramanian discloses a process for preparing N-phosphonomethylglycine, a secondary amine, by reacting an alkali metal hydroxide with N-(diethylphosphonomethyl)iminobisethanol, a tertiary amine, in the presence of a zinc oxide or cadmium oxide catalyst, and thereafter acidifying the product formed.
Now, a process has been discovered by which substituted or unsubstituted alkyl groups can be removed from secondary or tertiary amines to yield the corresponding primary or secondary amine, respectively. The dealkylation process of the present invention is useful, not only in the context of the removal of an alkyl amine-protecting group, but also in the synthesis of selected primary or secondary amines in which the precursor compound is one containing an alkyl-substituted amine group. Another distinct advantage is the lack of requirement for a heavy metal catalyst in the reaction mixture, which eliminates the cost and handling of such a catalyst, and also the problems associated with contamination of the product and waste streams by said heavy metal catalyst.